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PURPOSE: This prospective study evaluates whether rituximab is a safe and potentially effective treatment for nonparaneoplastic autoimmune retinopathy (npAIR). MATERIALS AND METHODS: Five npAIR patients were enrolled in a Phase I/II, prospective, nonrandomized, open-label, single-center study. All patients received a cycle of 1000 mg intravenous rituximab at weeks 0 and 2, with a second cycle of rituximab 6 to 9 months later. Clinical evaluation was performed at baseline, 6 and 12 weeks after each rituximab cycle, and then every 3 months for a total duration of 18 months. The primary outcome for this study was treatment success based on visual field and full-field electroretinography at 6 months. The secondary outcomes included treatment success at months 12 and 18, drug-related adverse events, changes in visual symptoms, and changes in quality of life. RESULTS: Two patients met criteria for treatment success: one based solely on electroretinography and the other based solely on visual field area, but treatment success was not sustained. Clinical response over the course of the 18-month study showed disease stabilization in three patients and treatment failure in two patients. There were no severe drug-related adverse events. CONCLUSION: This is the first clinical trial prospectively evaluating the effect of rituximab in npAIR and, although rituximab was well tolerated, there was no clear-cut clinical improvement conferred by B cell depletion with rituximab.

Purpose: Aims to determine the variability of ffERG measurements in patients with clinically stable birdshot chorioretinopathy (BCR). Methods: Repeatability coefficients (RC) of ffERG amplitudes and implicit times were calculated from 11 BCR patients. Jackknife resampling estimated 95% confidence intervals of each ERG parameter���s RC and the percentage change explained by variability alone was calculated. Results: Intra-visit variability in ffERG parameters was lower than inter-visit. Intravisit RCs demonstrated that for intravisit ERG testing, there was less than 30% variation in ERG amplitude for most parameters. For inter-visit ERG testing, a greater than 40% reduction in ERG amplitude may be clinically meaningful for 6 of 8 ERG parameters. Photopic single flash responses have Conclusions: A 40% reduction in ERG amplitude and/or a delay of >2 msec in the photopic single flash response may be suitable criteria for meaningful change in BCR patients.

The International Society for the Clinical Electrophysiology of Vision (ISCEV) standard for full-field electroretinography (ERG) describes a minimum set of tests, but encourages the use of additional protocols for clinical ERG testing. This extended protocol describes recording methods and derivations that will allow analysis of rod-driven components of the dark-adapted (DA) strong flash ERG a-wave, more closely related to rod phototransduction than ISCEV standard DA ERGs. The method involves recording ERGs to a flash strength equivalent to 30 cd s m2 under conditions of dark adaptation and additionally to the same stimulus following light adaptation (LA) and in the presence of a standard photopic background luminance of 30 cd m−2. The isolated rod-driven ERG a-wave is derived by subtracting the LA response from the DA ERG. The method is likely to be of value in the characterization of retinal disorders which affect rod quantal catch, diseases that affect the dynamics of any component of the activation phase of rod phototransduction, or those affecting total numbers of rod photoreceptors.

BACKGROUND. Oculocutaneous albinism (OCA) results in reduced melanin synthesis, skin hypopigmentation, increased risk of UV-induced malignancy, and developmental eye abnormalities affecting vision. No treatments exist. We have shown that oral nitisinone increases ocular and fur pigmentation in a mouse model of one form of albinism, OCA-1B, due to hypomorphic mutations in the Tyrosinase gene. METHODS. In this open-label pilot study, 5 adult patients with OCA-1B established baseline measurements of iris, skin, and hair pigmentation and were treated over 12 months with 2 mg/d oral nitisinone. Changes in pigmentation and visual function were evaluated at 3-month intervals. RESULTS. The mean change in iris transillumination, a marker of melanin, from baseline was 1.0 ± 1.54 points, representing no change. The method of iris transillumination grading showed a high intergrader reliability (intraclass correlation coefficient ≥ 0.88 at each visit). The number of letters read (visual acuity) improved significantly at month 12 for both eyes (right eye, OD, mean 4.2 [95% CI, 0.3, 8.1], P = 0.04) and left eye (OS, 5 [1.0, 9.1], P = 0.003). Skin pigmentation on the inner bicep increased (M index increase = 1.72 [0.03, 3.41], P = 0.047). Finally, hair pigmentation increased by both reflectometry (M index [17.3 {4.4, 30.2}, P = 0.01]) and biochemically. CONCLUSION. Nitisinone did not result in an increase in iris melanin content but may increase hair and skin pigmentation in patients with OCA-1B. The iris transillumination grading scale used in this study proved robust, with potential for use in future clinical trials. TRIAL REGISTRATION. ClinicalTrials.gov NCT01838655. FUNDING. Intramural program of the National Eye Institute., Oral nitisinone may improve melanin pigmentation in patients with the OCA-1B form of albinism due to hypomorphic mutations in the tyrosinase gene.

Author(s): Cukras, Catherine A; Huryn, Laryssa A; Jeffrey, Brett G; Turriff, Amy; Sieving, Paul A | Abstract: PurposeTo examine the symmetry of structural and functional parameters between eyes in patients with X-linked retinoschisis (XLRS), as well as changes in visual acuity and electrophysiology over time.MethodsThis is a single-center observational study of 120 males with XLRS who were evaluated at the National Eye Institute. Examinations included best-corrected visual acuity for all participants, as well as ERG recording and optical coherence tomography (OCT) on a subset of participants. Statistical analyses were performed using nonparametric Spearman correlations and linear regression.ResultsOur analyses demonstrated a statistically significant correlation of structural and functional measures between the two eyes of XLRS patients for all parameters. OCT central macular thickness (n = 78; Spearman r = 0.83, P l 0.0001) and ERG b/a ratio (n = 78; Spearman r = 0.82, P l 0.0001) were the most strongly correlated between a participant's eyes, whereas visual acuity was less strongly correlated (n = 120; Spearman r = 0.47, P l 0.0001). Stability of visual acuity was observed with an average change of less than one letter (n = 74; OD -0.66 and OS -0.70 letters) in a mean follow-up time of 6.8 years. There was no statistically significant change in the ERG b/a ratio within eyes over time.ConclusionsAlthough a broad spectrum of clinical phenotypes is observed across individuals with XLRS, our study demonstrates a significant correlation of structural and functional findings between the two eyes and stability of measures of acuity and ERG parameters over time. These results highlight the utility of the fellow eye as a useful reference for monocular interventional trials.

This study evaluated the safety and tolerability of ocular RS1 adeno-associated virus (AAV8-RS1) gene augmentation therapy to the retina of participants with X-linked retinoschisis (XLRS). XLRS is a monogenic trait affecting only males, caused by mutations in the RS1 gene. Retinoschisin protein is secreted principally in the outer retina, and its absence results in retinal cavities, synaptic dysfunction, reduced visual acuity, and susceptibility to retinal detachment. This phase I/IIa single-center, prospective, open-label, three-dose-escalation clinical trial administered vector to nine participants with pathogenic RS1 mutations. The eye of each participant with worse acuity (≤63 letters; Snellen 20/63) received the AAV8-RS1 gene vector by intravitreal injection. Three participants were assigned to each of three dosage groups: 1e9 vector genomes (vg)/eye, 1e10 vg/eye, and 1e11 vg/eye. The investigational product was generally well tolerated in all but one individual. Ocular events included dose-related inflammation that resolved with topical and oral corticosteroids. Systemic antibodies against AAV8 increased in a dose-related fashion, but no antibodies against RS1 were observed. Retinal cavities closed transiently in one participant. Additional doses and immunosuppressive regimens are being explored to pursue evidence of safety and efficacy (ClinicalTrials.gov: NCT02317887).

Purpose To report the first case of melanoma-associated retinopathy (MAR) and underlying occult melanoma diagnosed based on the presence of serum transient receptor potential melastatin 1 (TRPM1) autoantibodies. Design Interventional case report with basic science correlation. Participants One patient with MAR. Intervention Testing for the presence of serum TRPM1 autoantibodies. Main Outcome Measures Diagnosis of an occult melanoma involving the axillary lymph nodes (unknown primary site) and MAR based on the presence of TRPM1 autoantibodies in the patient's serum. Results The patient's clinical exam was remarkable for mild intraocular inflammation in both eyes and retinal hemorrhages with an apparent choroidal neovascularization in the left eye, which was confirmed by fluorescein angiography and indocyanine green angiography testing. Humphrey visual field 30-2 SITA-fast (Humphrey Visual Field Analyzer, Carl Zeiss Meditec, Inc, Dublin, CA) demonstrated diffuse depression in both eyes out of proportion to the clinical exams, prompting electroretinography testing that revealed an electronegative response. Dark-adapted thresholds were markedly elevated and mediated by cones. Due to concern for MAR, a systemic work-up for melanoma was performed by the primary care physician that was unrevealing. Given our continued clinical suspicion for MAR, the patient's serum was sent for evaluation for TRPM1 autoantibodies. The patient's serum applied to normal human retina exhibited positivity in the inner nuclear layer. Application of the patient's serum to wild-type and TRPM1 knockout mouse retina revealed strongly labeled bipolar cells in the wild-type retina, but not in the TRPM1 knockout retina, indicating TRPM1-dependent immunoreactivity. The antigen was confirmed as TRPM1 by labeling of TRPM1-transfected human embryonic kidney 293 cells. Additional systemic work-up prompted by this finding resulted in identification of an occult metastatic melanoma involving the axillary lymph nodes with an unknown primary site. The patient underwent surgical excision of the occult melanoma without evidence of other sites of metastases. He also received intravenous immunoglobulin therapy and his vision has stabilized. Conclusions This is the first reported case of a melanoma-associated retinopathy diagnosed utilizing the innovative approach of testing for serum TRPM1 autoantibodies. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

The strongest evidence for beneficial effects of long-chain polyunsaturated fatty acid (LCPUFA) supplementation comes from measures of visual development. In particular, two measures of visual function, the electroretinogram (ERG) and grating acuity, have provided the primary basis for the addition of LCPUFA to infant formulas. However, the neural mechanisms underlying dietary effects on these visual functions are not well understood. Furthermore, the influence of dietary LCPUFA on other aspects of visual development is largely unknown. Additional measures of visual function would help to clarify the extent and nature of the effects of LCPUFA on the developing visual system, and several new methods promise to provide more detailed information about the sites of these effects. A number of recent reviews have described methods for visual assessment and the effects of infant LCPUFA supplementation on visual development. Therefore, the following review will emphasize newer developments in infant visual assessment and in understanding the neural mechanisms that may underlie the effects of LCPUFA.

Circular contour frequency (the number of radial cycles per degree of unmodulated contour length measured in degrees of viewing angle) is an important factor in determining the deformation threshold of radial frequency (RF) patterns. Radial deformation thresholds were closely matched at a given circular contour frequency regardless of RF or radius. Our results suggest that two separate mechanisms may be involved in determining radial deformation thresholds. First, for low RFs, our results support a model of shape discrimination in which global integration occurs across all modulation cycles of an RF pattern. Second, for higher RFs, our data suggest that threshold may be determined by visual integration only over a limited segment of the RF pattern.

New outcome measures for treatment trials for Stargardt disease type 1 (STGD1) and other macular diseases are needed. Microperimetry allows mapping of light sensitivity of the macula and provides topographic information on visual function beyond visual acuity.To measure and analyze retinal light sensitivity of the macula in STGD1 using fundus-controlled perimetry (microperimetry).This was a multicenter prospective cohort study. A total of 199 patients and 326 eyes with molecularly confirmed (ABCA4) STGD1 underwent testing with the Nidek MP-1 microperimeter as part of the multicenter, prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study. Sensitivity of 68 retinal loci was tested, and the mean sensitivity (MS) was determined; each point was categorized as "normal," "relative," or "deep" scotoma.Mean sensitivity and the number of points with normal sensitivity, relative, or deep scotomas.Mean (SD) patient age was 34.2 (14.7) years, mean (SD) best-corrected visual acuity of all eyes was 47.8 (16.9) Early Treatment Diabetic Retinopathy Study letter score (approximately 20/100 Snellen equivalent), and mean MS of all eyes of all 68 points was 11.0 (5.0) dB. The median number of normal points per eye was 49 (mean [SD], 41.3 [20.8]; range, 0-68); abnormal sensitivity and deep scotomas were more prevalent in the central macula. Mean sensitivity was lower in the fovea (mean [SD], 2.7 [4.4] dB) than in the inner (mean [SD], 6.8 [5.8] dB) and outer ring (mean [SD], 12.7 [5.3] dB). Overall MS per eye was 0.086 dB lower per year of additional age (95% CI, -0.13 to -0.041; P .001) and 0.21 dB lower per additional year of duration of STGD1 (95% CI, -0.28 to -0.14; P .001). Longer duration of STGD1 was associated with worse MS (β = -0.18; P .001), with a lower number of normal test points (β = -0.71; P .001), and with a higher number of deep scotoma points (β = -0.70; P .001). We found 11 eyes with low MS (6 dB) but very good best-corrected visual acuity of at least 72 Early Treatment Diabetic Retinopathy Study letter score (20/40 Snellen equivalent).We provide an extensive analysis of macular sensitivity parameters in STGD1 and demonstrate their association with demographic characteristics and vision. These data suggest microperimetry testing provides a more comprehensive assessment of retinal function and will be an important outcome measure in future clinical trials.

BackgroundInherited retinal diseases are uncommon, and the likelihood of having more than one hereditary disorder is rare. Here, we report a case of Stargardt disease and congenital stationary night blindness (CSNB) in the same patient, and the identification of two novel in-frame deletions in the GRM6 gene.Materials and methodsThe patient underwent an ophthalmic exam and visual function testing including: visual acuity, color vision, Goldmann visual field, and electroretinography (ERG). Imaging of the retina included fundus photography, spectral-domain optical coherence tomography (OCT), and fundus autofluorescence. Genomic DNA was PCR-amplified for analysis of all coding exons and flanking splice sites of both the ABCA4 and GRM6 genes.ResultsA 46-year-old woman presented with recently reduced central vision and clinical findings of characteristic yellow flecks consistent with Stargardt disease. However, ERG testing revealed an ERG phenotype unusual for Stargardt disease but consistent with CSNB1. Genetic testing revealed two previously reported mutations in the ABCA4 gene and two novel deletions in the GRM6 gene.ConclusionsDiagnosis of concurrent Stargardt disease and CSNB was made on the ophthalmic history, clinical examination, ERG, and genetic testing. This case highlights that clinical tests need to be taken in context, and that co-existing retinal dystrophies and degenerations should be considered when clinical impressions and objective data do not correlate.

Purpose: To compare the effect of intensive and reduced occlusion therapy regimens on binocular sensory outcomes, visual acuity, and the prevalence of strabismus in children after surgery for congenital unilateral cataract. Methods: Two nonrandomized groups of patients were studied prospectively: (1) an intensive occlusion group (n = 29) patched 80% of waking hours were followed for a median 6.9 years and (2) a reduced occlusion group (n = 8) patched 25% to 50% of waking hours were followed for a median 4.3 years. Six subjects in the intensive group and 4 in the reduced occlusion group had secondary intraocular lenses. Two subjects in the intensive group had epikeratophakia surgery. Binocular sensory function was assessed with random dot and contour stereoacuity tests and the Worth 4-dot test. The prevalence and age at onset of strabismus were determined from the patients' charts. Results: A higher proportion of subjects in the reduced occlusion group (50%) had stereoacuity or fusion compared with the intensive occlusion group (14%), a borderline significant difference ( P = .08). No significant difference ( P = .55) was found in median visual acuity between the intensive (20/50) and the reduced occlusion (20/55) groups. The 90% prevalence of strabismus in the intensive occlusion group was slightly higher than the 63% prevalence in the reduced occlusion group, although this difference was not significant ( P = .18). Conclusions: These results suggest that a reduced occlusion protocol may be associated with better binocular sensory outcomes and a reduced prevalence of strabismus without compromising good visual acuity in children treated for congenital unilateral cataract. (J AAPOS 2001;5:209-16)

Background There are nutritional recommendations that the ratio of linoleic to alpha-linolenic acid (LA:ALA) in formula for term infants be between 5:1 and 15:1. These recommendations were made in the absence of data on functional or clinical outcomes. Objective We compared the fatty acid status, visual evoked potential (VEP) acuity, and growth of term infants fed formula containing an LA:ALA of 10:1 or 5:1 with those of a breast-fed reference cohort. Design Formula-fed infants were allocated randomly in a double-blind fashion to receive formula with an LA:ALA of either 10:1 (16.9:1.7; n = 36) or 5:1 (16.3:3.3; n = 37) from near birth to 34 wk of age. Increased ALA was attained by replacing soy oil with low-erucic acid cannola oil. A parallel group of breast-fed infants was also recruited. Infant growth and fatty acid status were assessed at 6, 16, and 34 wk of age. VEP acuity was assessed at 16 and 34 wk. Results Infants fed the 5:1 formula had greater docosahexaenoic acid (DHA) concentrations in plasma and erythrocyte phospholipids than did infants fed the 10:1 formula, but DHA concentrations of infants fed the 5:1 formula remained less than those in breast-fed infants. The VEP acuity of all formula-fed and breast-fed infants was not significantly different at 16 and 34 wk of age. At birth, infants fed the 5:1 formula were heavier, were longer, and had a greater head circumference than infants assigned to the 10:1 formula group; this differential was maintained throughout the trial. The rate of gain in weight, length, and head circumference was not significantly different between the 2 formula-fed groups, although breast-fed infants had lower weight and length gains than did formula-fed infants between 16 and 34 wk of age. Conclusion Lowering the LA:ALA in formula from 10:1 to 5:1 by using low-erucic acid canola oil resulted in a modest increase in plasma DHA but had no effect on VEP acuity or growth rate.

Alport's syndrome is characterised by progressive haematuric nephritis and high tone sensorineural hearing loss. Ocular signs are variable, the most consistent findings being anterior lenticonus and retinal flecks in the macula and mid peripheral areas. Previous electrophysiological studies on patients with Alport's syndrome have mostly been on adult patients undergoing haemodialysis, or after renal transplantation. A group of young patients with Alport's syndrome were studied to assess if early electrophysiological changes were detectable. A total of 20 patients (15 males and five females) between the ages of 3.5 and 22 years (mean 12.7 (years) were examined and compared with control subjects. Visual evoked potentials and electroretinograms were obtained following flash and pattern reversal stimulation. Electro-oculograms were also recorded. No significant electrophysiological changes were found in any of the 20 patients, including four who had visible fundus changes.

Background: Alport syndrome is an X-linked disease affecting basement membrane collagen. It is characterized by nephritis associated with high-tone sensorineural hearing impairment and ophthalmic signs. Although ocular changes have been described in adults, few data exist regarding the incidence of abnormal ocular features in adolescence and childhood. Methods: Fifteen male and five female patients with Alport syndrome underwent ophthalmologic, audiologic, and nephrologic assessments. All patients studied had hematuria and a positive family history of Alport syndrome. Thirteen patients had a renal biopsy that showed characteristic electron microscopic changes of the disease. Eleven patients had high-tone sensorineural impairment. Electrophysiologic investigations performed included electroretinography, visual-evoked potentials, and electro-oculography. Results: Two patients had early signs of anterior lenticonus, three had flecks in the retina, and two patients also had posterior subcapsular cataracts. None of the patients had significant electrophysiologic abnormalities. Conclusion: These findings indicate that ocular changes are uncommon and subtle in young patients with Alport syndrome, and suggest that the signs increase in frequency and severity with age.

We review the epidemiology, aetiology, pathogenetic mechanisms and clinical management of neonatal cataract. Visual development and the effects of visual deprivation in the infant with congenital cataract are discussed and related to the timing of surgery. Surgical techniques and the important operative and post-operative complications are discussed. We review post-operative management and compare the different techniques available for aphakic correction, and describe the VEP changes found in patients with monocular cataract.

Purpose: The aim of the present study was to develop a simple, quick, and portable random dot stereoacuity test for measurement of binocular sensory outcomes during the first 24 months of life. Methods: Vertical bar random dot vectographs were adapted for presentation in a "Teller Acuity Card" format, called the "Randot® Stereocards." A forced-choice preferential looking protocol was used. Study participants included 386 healthy, term infants and children (normative cohort; age range: 1 month to 8 years) and 280 patients with common pediatric ophthalmic disorders (patient cohort; age range: 5 months to 9 years). Results: Overall, the success rate for test completion in the normative cohort was 91.3%. By 4 months of age, normal infants' mean stereoacuity was about 600″ and, by 6 months, 200″. Mean stereoacuity further improved to about 100″ by 12 months and 70″ by 18 months. Normative results were similar to published data obtained with laboratory-based stereoacuity tests. Randot® Stereocard data from normal children aged 2 to 6 years were similar to published normative data for the Preschool Randot® Stereoacuity Test. In the patient cohort, concordance between the Randot® Stereocards and the Preschool Randot® Test was 87%; concordance between the Randot® Stereocards and the Randot® Test was 84%. Conclusion: The Randot® Stereocards provide a simple, reliable, and valid method of obtaining a quantitative assessment of binocular vision in children up to 24 months of age for use in clinical trials and in clinical management.

The Worth 4-Dot is used to assess binocular fusion, but it is difficult to use with young children. We modified the Worth 4-Dot by replacing the circles with shapes while maintaining the same color configuration. The purpose of this study was to determine the testability, reliability, and validity of the Worth 4-Shape test.Subjects aged 2 to 8 years and 4 patients aged over 8 years with best-corrected visual acuity of 20/40 or greater (n = 131 patients, n = 123 normals) attempted test and retest at 35 cm and 3m using the Worth 4-Shape and Worth 4-Dot. To provide a gold standard, medical history, bifoveal fixation, and stereoacuity were reviewed.Testability of the Worth 4-Shape was significantly higher than the Worth 4-Dot both in children aged less than 4 years (95.9% vs 79.5% at 35 cm, P.001; 79.5% vs 55.1% at 3 m, P.001) and older than 4 years (98.5% vs 88.6% at 35 cm, P.001; 90.9% vs 82.4% at 3m, P =.04). Test-retest analysis found comparable concordance for the Worth 4-Shape and Worth 4-Dot tests (P.3). The sensitivity and specificity of the Worth 4-Shape (92%, 97%) and Worth 4-Dot (90%, 94%) were comparable. Between-test analysis found 96% agreement between both tests at 35 cm and 97% agreement at 3m.The success rate for the Worth 4-Shape is higher than the Worth 4-Dot, especially in children aged less than 4 years, and has equivalent accuracy. The Worth 4-Shape test-retest reliability is high supporting its validity for use with young children.

To compare patching and atropine as treatments for moderate amblyopia in children younger than 7 years.In a randomized clinical trial, 419 children younger than 7 years with amblyopia and visual acuity in the range of 20/40 to 20/100 were assigned to receive either patching or atropine at 47 clinical sites.Visual acuity in the amblyopic eye and sound eye after 6 months.Visual acuity in the amblyopic eye improved in both groups (improvement from baseline to 6 months was 3.16 lines in the patching group and 2.84 lines in the atropine group). Improvement was initially faster in the patching group, but after 6 months, the difference in visual acuity between treatment groups was small and clinically inconsequential (mean difference at 6 months, 0.034 logMAR units; 95% confidence interval, 0.005-0.064 logMAR units). The 6-month acuity was 20/30 or better in the amblyopic eye and/or improved from baseline by 3 or more lines in 79% of the patching group and 74% of the atropine group. Both treatments were well tolerated, although atropine had a slightly higher degree of acceptability on a parental questionnaire. More patients in the atropine group than in the patching group had reduced acuity in the sound eye at 6 months, but this did not persist with further follow-up.Atropine and patching produce improvement of similar magnitude, and both are appropriate modalities for the initial treatment of moderate amblyopia in children aged 3 to less than 7 years.

Purpose Ciliary neurotrophic factor (CNTF) protects rod photoreceptors from retinal degenerative disease in multiple nonhuman models. Thus far, CNTF has failed to demonstrate rod protection in trials for human retinitis pigmentosa. Recently, CNTF was found to improve cone photoreceptor function in a canine CNGB3 achromatopsia model. This study explores whether this finding translates to humans with CNGB3 achromatopsia. Methods A five-subject, open-label Phase I/II study was initiated by implanting intraocular microcapsules releasing CNTF (nominally 20 ng/d) into one eye each of CNGB3 achromat participants. Fellow eyes served as untreated controls. Subjects were followed for 1 year. Results Pupil constriction in treated eyes gave evidence of intraocular CNTF release. Additionally, scotopic ERG responses were reduced, and dark-adapted psychophysical absolute thresholds were increased, attributable to diminished rod or rod pathway activity. Optical coherence tomography revealed that the cone-rich fovea underwent structural changes as the foveal hyporeflective zone (HRZ) became diminished in CNTF-treated eyes. No objectively measurable enhancement of cone function was found by assessments of visual acuity, mesopic increment sensitivity threshold, or the photopic ERG. Careful measurements of color hue discrimination showed no change. Nonetheless, subjects reported beneficial changes of visual function in the treated eyes, including reduced light sensitivity and aversion to bright light, which may trace to decreased effective ambient light from the pupillary constriction; further they noted slowed adaptation to darkness, consistent with CNTF action on rod photoreceptors. Conclusions Ciliary neurotrophic factor did not measurably enhance cone function, which reveals a species difference between human and canine CNGB3 cones in response to CNTF. (ClinicalTrials.gov number, NCT01648452.).

Electroretinography (ERG), especially when combined with visual evoked potential recording, can provide valuable information to the pediatric clinician assessing a young child with nystagmus who appears not to see. ERG changes are described in clinical conditions affecting rod and/or cone function, vitreoretinal disease, maculopathies, and disorders involving the retina and central nervous system. The role of ERG in monitoring treatment, and in excluding retinal disease prior to eye surgery, is also covered.